三七总皂苷对慢性马兜铃酸肾病大鼠体内抗氧化作用的研究

目的观察三七总皂苷对慢性马兜铃酸肾病损害大鼠模型抗氧化作用。方法 Wistar大鼠随机分为正常对照组、模型组及三七总皂苷低、中、高剂量组。造模大鼠按马兜铃酸20 mg.kg-1.d-1的剂量灌服关木通浸膏,1周后改为按马兜铃酸15 mg.kg-1.d-1的剂量灌服,4 h后三七总皂苷各组灌服不同剂量三七总皂苷溶液(100、200、400 mg.kg-1.d-1),模型组灌服等体积生理盐水。分别于实验第12、16、20周测定大鼠肾组织SOD活性、MDA含量及GHS含量。结果三七总皂苷可升高慢性马兜铃酸肾病大鼠肾组织SOD活性和GSH-PX含量,明显降低肾组织中MDA(P<0.05)。结论三七总皂苷对慢性马兜铃酸肾病大鼠损伤起保护作用。     

小鼠脑缺血后的能量代谢改变和药物的作用

应用部分结扎小鼠颈总动脉(包括迷走神经)及小鼠断头法引起脑缺血后,脑组织的ATP和磷酸肌酸明显降低,乳酸明显升高。部分结扎颈动脉出现四肢无力、转圈及昏睡等症状,其严重程度与脑能量代谢改变相平行。皮下注射尼莫地平、硝苯吡啶、尼卡地平和三七皂甙对脑缺血有一定保护作用。苯巴比妥钠能改善正常和脑缺血小鼠的脑能量代谢,人参皂甙Rb₁可降低正常小鼠脑乳酸含量。     

三七皂甙Rb对实验性脑梗死大鼠全血碳氧血红蛋白的影响

目的研究三七皂甙Rb1对大鼠脑梗死后全血碳氧血红蛋白及梗死面积的影响。方法采用SD雄性大鼠,通过栓塞大脑中动脉并于1h后再灌注复制局灶性缺血再灌注损伤模型。通过生化检测、免疫组织化学染色等方法观察脑缺血再灌注损伤后全血碳氧血红蛋白(COHb)含量以及不同剂量的三七皂甙Rb1对COHb的含量等方面的影响。结果①脑缺血再灌注损伤后,模型组的全血碳氧血红蛋白含量显著高于假手术组(P<0.05),并在再灌注24h达到一个高峰。②给予中剂量三七皂甙Rb1(10mg/kg)与模型组相比可显著升高脑缺血再灌注损伤后全血碳氧血红蛋白含量(P<0.05)。结论大鼠脑缺血再灌注损伤后全血碳氧血红蛋白含量显著升高。三七皂甙Rb1通过增加COHb含量改善脑缺血再灌注后的脑损伤,并减小脑梗死的体积。本研究为今后对脑梗死的治疗和科研可能提供了一个崭新的思路。     

三七皂甙Rb_1、Rg_1对大鼠心肌缺血再灌注心律失常的保护作用

<正> 三七根总皂甙主要含皂甙和少量黄酮,三七皂甙Rb_1、Rg_1为从三七根总皂甙中提取的人参三醇,人参二醇衍生单体。本研究在大鼠造成心肌缺血再灌注心律失常模型,观察三七皂甙单体Rb_1、Rg_1的保护效应,为探讨其作用机制并与自由基清除剂超氧化物歧化酶(SOD)进行比较。     

三七总皂苷鼻用凝胶喷雾剂的药动学与药效学研究

目的研究自制三七总皂苷鼻用凝胶喷雾剂的生理适应性、家兔给药后体内的药动学过程,及其对心血管疾病的保护作用。方法选用扫描电镜法,考察喷雾剂的鼻纤毛毒性;HPLC法测定三七总皂苷鼻用凝胶喷雾剂家兔鼻腔给药后血样中人参皂苷Rb1、Rg1的浓度,考察药物在体内的动力学过程,并计算药动学参数;建立大鼠急性缺血性心肌梗死模型,考察三七总皂苷鼻用凝胶喷雾剂对心脑血管疾病的保护作用。结果三七总皂苷鼻用凝胶喷雾剂给药后,Rb1、Rg1在家兔体内的过程符合二室模型,其绝对生物利用度比三七总皂苷滴鼻液高,分别为（42．31±7．54）％和（81．06±32．71）％;可大幅减少大鼠左冠状动脉闭塞所致的心肌梗死面积,且呈剂量依赖性,剂量越高,保护作用越强;该喷雾剂基本无明显鼻纤毛毒性。结论药动学、药效学及鼻纤毛毒性试验结果证明,三七总皂苷鼻腔给药制剂具有很好的开发前景。     

三七总皂苷鼻腔给药的药代动力学与药效学

目的研究三七总皂苷鼻腔用粉雾剂以混悬液形式给药后在大鼠体内的药代动力学过程及对心脑血管疾病的保护作用。方法HPLC测定三七总皂苷混悬液大鼠鼻腔给药后血样中人参皂苷Rg1的浓度，考察药物在体内的动力学过程，并计算其绝对生物利用度；结扎SD大鼠的左冠状动脉建立急性缺血性心肌梗死模型，夹闭沙鼠的双侧颈总动脉建立脑缺血再灌注模型，考察三七总皂苷混悬液对心脑血管疾病的保护作用。结果三七总皂苷混悬液鼻腔给药后，Rg1在大鼠体内的过程符合二室模型，其绝对生物利用度为103.56％；对大鼠急性缺血性心肌梗死及沙鼠脑缺血再灌注所引起的脑水肿和脑卒中症状均具有明显的缓解作用，且呈剂量依赖性，剂量越高，保护作用越强。结论药代动力学和药效学结果证明，三七总皂苷鼻腔给药制剂具有很好的开发前景。     

生姜对脑缺血再灌注损伤防治作用的探讨

在家兔急性完全性脑缺血模型上，观察了生姜的脑复苏效应，结果表明：生姜能显著地增高和降低ＳＯＤ活性和ＭＤＡ含量，同时并能保护再灌时Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶的活性和减轻缺血再灌注性脑水肿。提示：生姜具有明显地防治脑缺血再灌注损伤的作用。     

小鼠暂时性脑缺血引起学习记忆障碍模型的制备及人参皂甙的保…

人参皂甙是人参的主要有效成分。本文在建立小鼠脑缺血再灌注导致学习记忆障碍模型的基础上，用跳台、避暗两种实验方法观察了人参皂甙对小鼠脑缺血再灌注后学习记忆功能的保护作用。结果显示小鼠脑缺血再灌注可以导致学习记忆障碍，而人参皂甙可以对这种记忆障碍起到保护作用。     

三七总皂甙提取工艺研究进展

三七总皂甙（PNS）（又称三七总皂苷）为五加科人参属植物三七根部提取的有效成分,它含有人参皂甙Rb1、Rb2、Rc、Rd、Re、Rf、Rg1、Rg2、Rh、三七皂甙R1、1／2、R3、R4、R5、R6等20多种皂甙成分,其中以人参皂甙Rb1、Rg1、三七皂甙R1含量最高Ⅲ。三七总皂甙对中枢神经系统有明显的抑制作用和镇痛作用。     

三七皂甙组分镇痛作用的研究

三七皂甙是三七的主要化学成价,系由Rb组和Rg组皂甙组成。本文对三七皂甙组分的镇痛作用进行了实验观察。实验材料三七总皂甙、三七皂甙Rb组和Rg组均由昆明植物研究所提供。Rb组主要含人参皂甙Rb_1及少量Rb_2,Rc和Rd;Rg组主要含人参皂甙Rg_1及少量Rg_2、Rf和两种三七新皂甙。实验时以生理盐水将三七总皂甙和Rb组配成所需浓度,Rg组以2％吐温-80生理盐水配制。     

绞股蓝总皂甙对家兔急性不完全性脑缺血的保护作用

绞股蓝总皂甙(50mg·kg~(-1))可明显改善家兔脑缺血60 min后的脑电图变化,降低脑静脉血中LDH和CPK活性,改善缺血后脑组织形态学变化,提示绞股蓝总皂甙对脑缺血有保护作用。     

黄蜀葵总黄酮对全脑缺血损伤的保护作用

目的　研究黄蜀葵总黄酮 (TFA)对脑缺血及再灌注损伤的保护作用。方法　结扎双侧颈总动脉建立小鼠脑缺血模型 ,观察小鼠 6h存活率 ,测定缺血脑组织中丙二醛(MDA)含量 ;采用小鼠氮气缺氧模型 ,观察小鼠存活时间 ;采用结扎双侧颈总动脉合并血压下降法建立兔脑缺血再灌注模型 ,兔脑缺血 60min后再灌注 3 0min ,记录脑缺血和再灌注的脑电图 (EEG) ,测定缺血脑组织的丙二醛 (MDA)、乳酸脱氢酶 (LDH)。结果　TFA(3 0、60、12 0mg·kg-1)延长小鼠缺氧后的存活时间和提高脑缺血后小鼠的存活率及能抑制脑组织中MDA的增高。TFA(12、2 4、48mg·kg-1)抑制兔脑缺血再灌注损伤所致的EEG、MDA、LDH变化。结论　TFA对脑缺血及再灌注损伤有保护作用 ,其机制可能与抗自由基和脂质过氧化有关     

化学诱导兔脑缺血模型早期MSCT灌注成像实验性研究

目的应用化学诱导方法建立稳定可靠的兔脑局部缺血模型,探讨早期缺血性脑梗死多层螺旋CT（MSCT）灌注成像表现与最终梗死体积的关系。方法对34只健康新西兰大白兔成功栓塞,然后分别于栓塞后15min、30min、1h行MSCT灌注成像扫描,2、4、6、8、10、12、24h行颅脑CT平扫观察。结果应用月桂酸钠化学诱导方法成功建立稳定、可靠的脑局部缺血模型,经病理HE染色证实神经元变性坏死明显,大量神经元固缩,并可见到神经元周围空泡样改变。MSCT灌注成像表现：实验兔梗塞后20～30minCT脑血流量（CBF）灌注图可以清楚地显示不同程度的缺血状态,兔脑两侧相比有明显的色阶变化,一侧大脑半球局部呈低灌注状态。继续跟踪观察2、4、6、8、10、12、24hCT平扫发现大部分最终梗死体积与灌注图像获得的梗死范围基本一致。结论应用月桂酸钠化学诱导方法可成功建立稳定可靠的脑梗死模型,MSCT灌注扫描CBF灌注图像可最早于梗死后15～20min发现脑梗死病灶,并且大部分与最终梗死体积基本一致。     

苯环利定对兔急性脑缺血损伤的保护作用——脑脊液中β-内啡肽免疫活性分析

结扎兔双侧椎动脉和颈总动脉,导致急性脑缺血。缺血30min后重新开放双侧颈总动脉,使再灌注。脑缺血30min再灌注2h后,脑脊液中β—内啡肽免疫活性物质含量比缺血前增加1.01±0.52mg/L。icv苯环利定20μg/kg组,脑脊液中β—内啡肽免疫活性物质含量比缺血前增加0.36±0.32mg/L。icv苯环利定80μg/kg组,脑脊液中β—内啡肽免疫活性物质含量比缺血前下降0.19±0.44mg/L。提示苯环利定能抑制脑缺血后脑内β—内啡肽释放,减轻脑缺血性神经损伤。     

大蒜新素对实验性急性脑缺血的保护作用

大蒜新素对实验性急性脑缺血的保护作用马晓红１刘天培（南京医科大学药理学教研室，南京２１００２９）大蒜新素（ａｌｉｔｒｉｄｉ，Ａｌ）为葱科植物大蒜中的有效成分，已发现其有降压，降血脂，抗动脉粥样硬化，抗血小板聚集及抗心肌缺血等作用［１，２］．临床上有关...     

Protecting mechanism of puerarin on the brain neurocyte of rat in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury

The present study was designed to investigate the possible properties of the injured brain neurocytes, the expression of heat shock protein70 (HSP70) and Fas protein after acute local ischemia brain injury and local cerebral ischemia-reperfusion injury in rats and to investigate the protecting mechanism of puerarin on the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury. A rat model of acute local cerebral ischemia was made by ligatting the middle cerebral artery. The rat model of local cerebral ischemia and reperfusion injury was made by ligatting the middle cerebral artery for 30 min then opened for 30 min. Rats of puerarin treating group were injected with puerarin in dose of 30 mg/kg(-1) by intraperitoneal injection 30 min before ischemia. HSP70 and Fas protein expressions in brain tissue were detected by SP method of histochemistry. In addition, dead brain neurocytes were counted and their morphology was observed. The results indicated that puerarin can limit the tissue injury caused by local cerebral ischemia injury through improving expression of HSP70, and limit the tissue injury caused by local cerebral ischemia-reperfusion through decreasing the Fas expression and improving expression of HSP70. On the basis of these results, it may be concluded that puerarin can protect the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury, which may be different according to the different injury mechanism.     

白三烯拮抗剂ONO-1078对小鼠持续性局灶性脑缺血的作用

目的在小鼠模型研究白三烯拮抗剂{4-氧-8-[对-(4-苯丁氧基)苯甲酰氨基]-2-(5-四唑基)-4H-1-苯并吡喃半水合物(ONO-1078)}对脑缺血的保护作用.方法以大脑中动脉阻塞法诱导持续性局灶性脑缺血.在脑缺血前30min和缺血后60min腹腔注射ONO-1078、尼莫地平或生理盐水(对照).脑缺血24h后,观察神经症状,并测定脑湿重和脑梗死体积.结果ONO-1078(0.01,0.03,0.1mgkg-1)和尼莫地平(0.2 mg*kg-1)减少脑梗死体积;ONO-1078(0.1 mg kg-1)减轻脑湿重,尼莫地平无此作用;ONO-1078和尼莫地平对神经症状无明显作用.结论ONO-1078对持续性局灶性脑缺血有保护作用,提示白三烯拮抗剂可作为急性脑缺血的一种新治疗药.     

Possible involvement of ubiquitin proteasome system and other proteases in acute and delayed aspects of ischemic preconditioning of brain in mice

The present study has been designed to investigate the potential role of ubiquitin proteasome system and other proteases in acute as well as delayed aspects of ischemic preconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) both immediately before (for acute preconditioning) and 24 h before (for delayed preconditioning) global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. Z-Leu-Leu-Phe-Chinese hamster ovary (CHO) (2 mg/kg, intraperitoneally (i.p.)), an inhibitor of ubiquitin proteasome system and other proteases attenuated the neuroprotective effect of both the acute as well as delayed ischemic preconditioning. It is concluded that the neuroprotective effect of both the acute as well as delayed phases of ischemic preconditioning may be due to the activation of ubiquitin proteasome system and other proteases.     

Cilostazol, a phosphodiesterase 3 inhibitor, protects mice against acute and late ischemic brain injuries

Cilostazol, a selective inhibitor of phosphodiesterase 3, exerts neuroprotective effects on acute brain injury after cerebral ischemia in rats. However, it is unknown whether cilostazol affects the subacute or chronic ischemic injury. In the present study, we evaluated the dose- and time-dependent effects of cilostazol on acute ischemic brain injury and the long-lasting effect on the late (subacute/chronic) injury in mice with focal cerebral ischemia induced by transient middle cerebral artery occlusion. We found that pre-treatment of cilostazol (injected i.p. at 30 min before ischemia) significantly ameliorated the acute injury 24 h after ischemia, and the effective doses were 3-10 mg/kg. The post-treatment of cilostazol (10 mg/kg) was effective on the acute injury when it was injected 1 and 2 h after ischemia. In addition, for the late injury, post-treatment of cilostazol (10 mg/kg, i.p., for 7 consecutive days after ischemia) attenuated neurological dysfunctions, brain atrophy and infarct volume. It also inhibited astrocyte proliferation/glial scar formation and accelerated the angiogenesis in the ischemic boundary zone 7 and 28 days after ischemia. Thus, we conclude that cilostazol protects against not only the acute injury, but also the late injury in mice with focal cerebral ischemia; especially it can modify brain remodeling, astrogliosis and angiogenesis.